Guinea was officially declared Ebola-free, almost two years to the day after a toddler there became “Patient Zero,” the source of an outbreak that has killed more than 11,000 people, challenged health agencies and tested the responses of governments. (Associated ... more >

Liberia has twice declared victory over Ebola — and twice been surprised by subsequent outbreaks that have forced doctors and scientists to question what they really know about the deadly disease and its ability to spread.

Now the World Health Organization again has good news to deliver. Guinea was officially declared Ebola-free Tuesday, almost two years to the day after a toddler there became “Patient Zero,” the source of an outbreak that has killed more than 11,000 people, challenged health agencies and tested the responses of governments in Washington and around the world.

Officially, an outbreak is thought to be beaten if a country goes 42 days, or two 21-day incubation periods for the Ebola virus, without a new case.

Sierra Leone’s outbreak was declared over on Nov. 7, and the WHO is set to clear Liberia — again — on Jan. 14.

“This is the first time that all three countries — Guinea, Liberia and Sierra Leone — have stopped the original chains of transmission that were responsible for starting this devastating outbreak two years ago,” Dr. Matshidiso Moeti, WHO regional director for Africa, told reporters in Conakry, Guinea.

This West African nation will hold a major celebration Wednesday, overseen by President Alpha Conde and including testimonies by Ebola survivors. Later, popular West African artists such as Youssou N’Dour and Tiken Jah Fakoly are to perform at a concert in the capital.

But amid the celebrating, many are sounding a note of extreme caution, saying past declarations of victory have proven premature.

“This outbreak is not over. Forty-two days will not end this outbreak,” said William Fischer, an assistant professor of pulmonary and critical care medicine at the University of North Carolina, Chapel Hill, who cared for Ebola patients in West Africa.

Indeed, Liberia was first declared Ebola-free in May, after 5,000 deaths. But a new cluster of cases popped up in June, killing two more people.

The cycle repeated in the fall. Liberia was declared “Ebola-free” in September, and a 15-year-old died of the disease on Nov. 23. Even with Tuesday’s declaration, WHO officials say Guinea will remain under a 90-day period of heightened surveillance for a possible re-emergence of the disease.

“We definitely cannot let our guard down,” Dr. Tom Frieden, director of the Atlanta-based Centers for Disease Control and Prevention (CDC), said at Tuesday’s ceremony in Ghana. “It’s certainly possible we will have more cases and more clusters in the coming months.”

Ebola was first identified in 1976, but previous outbreaks had been small and limited to Africa. This new strain saw transmission in the U.S., and the stunning numbers of deaths — and survivors — have upended some of what scientists thought they knew about the virus and its ability to spread.

Earlier this year scientists documented a case in which the virus appeared to be transmitted by a survivor through sexual contact. And in October, the CDC reported that some male survivors in Sierra Leone produced semen samples with evidence of Ebola for nine months after their illness began.

The flare-ups in Liberia perplexed scientists, though reports at the time suggested the virus re-emerged through survivors. For example, the strains were more similar to ones that hit Liberia in 2014 than the strains that were still circulating in neighboring countries.

“It’s not completely clear what happened there,” said Dr. Marie-Paule Kieny, an assistant director general at WHO. “What is clear is that the measures we’re taking were sufficient to prevent broader community contamination.”

But Amesh Adalja, a senior associate at the University of Pittsburgh Center for Health Security, said the fact that transmission had been re-established after the country had been declared Ebola-free has several implications.

“One is that the sheer number of the infected creates a real risk of a shadow epidemic, in which all cases and transmission chains that are occurring are not known to public health authorities,” he said.

He said it can also mean that people exhibiting few or even no symptoms are still able to transmit the virus in some cases, and that infection by sexual transmission in particular will be difficult to control among the thousands of survivors.

Unraveling the ‘many unknowns’

Hoping to “unravel the many unknowns,” the U.S. National Institutes of Health has teamed with Liberia’s health ministry to study the long-term effects of Ebola on survivors. It is one of several efforts in the region sponsored by NIH, the CDC and WHO.

“Trying to understand this issue of viral persistence is one of the very important questions being addressed,” said Dr. Cliff Lane, clinical director at the National Institute of Allergy and Infectious Diseases.

So far the NIH study has enrolled 1,000 survivors and 600 of their close contacts, who will serve as a control group. For instance, survivors of Ebola are known to report problems with their vision, and scientists will be studying whether the vision problems and other health issues are linked to Ebola itself or to something else in the community.

On the homefront, U.S. officials stopped funneling travelers from Liberia through one of five major international airports — JFK in New York, Newark Liberty in New Jersey, Dulles in Washington, O’Hare in Chicago and Hartfield-Jackson in Atlanta — on Sept. 21 in light of progress in fighting the epidemic abroad.

Restrictions on travelers from Sierra Leone were lifted last week and those from Guinea will end by early February, or 45 days after WHO declares the country to be Ebola-free.

Spokeswoman Kristen Nordlund said the CDC did not reinstate rules on travelers from Liberia after November’s flare-ups because Liberian officials “responded to and controlled any further transmission.”

“In the event that new cases appeared in Liberia or Sierra Leone now, a decision to return a country to the ‘enhanced-screening’ list would be made after CDC experts assess how that country responds to and controls new cases, as well as after discussion and agreement among leaders of U.S. government agencies,” she said. “We can quickly reinstate enhanced screening measures if necessary.”

Meanwhile, scientists hoping to avoid a repeat of West Africa’s nightmare say a trial vaccine continues to show promise.

The vaccine, known in lab-speak as rVSV-ZEBOV, was developed by the Public Health Agency of Canada and licensed to NewLink Genetics Corp., which collaborated with pharmaceutical giant Merck.

Findings published in July reported that no one who received the vaccine during a WHO-sponsored trial developed Ebola after 10 days — the study’s cutoff for developing immunity from the injection — and officials say the vaccine maintained a perfect record since then.

“We are still very confident that that vaccine is effective,” Dr. Kieny said.

Merck spokeswoman Pamela Eisele said the company was “assembling the critical components” to apply for licensing rights from regulators, such as data on its effectiveness, safety, chemistry and how it’s made.

“Many of these data will not be available until late 2016, early 2017, but we are looking to accelerate the process wherever we can or where it is possible,” she said.